Ecomorphological variation in artiodactyl calcanei using 3D geometric morphometrics.

Artiodactyl postcrania are commonly used as paleoecological indicators but these studies are usually limited to artiodactyls within a single family. Here, we use 3D geometric morphometrics to analyze the morphology of calcanei from five artiodactyl families (Antilocapridae, Bovidae, Cervidae, Giraffidae, and Tragulidae) and identify common ecological trends among these families using principal component analysis. Our results indicate that antilocaprid and some bovid calcanei show convergent evolution of cursorial morphology and that other bovids have independently evolved less cursorial morphology that is more similar to cervids. This study shows that parallel ecomorphological trends can be identified in multiple families of artiodactyls, as well as within artiodactyl groups. This further suggests that the calcaneus may be a good indicator of ecology and function in fossil groups that are taxonomically ambiguous or not closely related to living taxa.

Ecological changes in Coyotes (Canis latrans) in response to the ice age megafaunal extinctions.

Coyotes (Canis latrans) are an important species in human-inhabited areas. They control pests and are the apex predators in many ecosystems. Because of their importance it is imperative to understand how environmental change will affect this species. The end of the Pleistocene Ice Age brought with it many ecological changes for coyotes and here we statistically determine the changes that occurred in coyotes, when these changes occurred, and what the ecological consequences were of these changes. We examined the mandibles of three coyote populations: Pleistocene Rancho La Brean (13-29 Ka), earliest Holocene Rancho La Brean (8-10 Ka), and Recent from North America, using 2D geometric morphometrics to determine the morphological differences among them. Our results show that these three populations were morphologically distinct. The Pleistocene coyotes had an overall robust mandible with an increased shearing arcade and a decreased grinding arcade, adapted for carnivory and killing larger prey; whereas the modern populations show a gracile morphology with a tendency toward omnivory or grinding. The earliest Holocene populations are intermediate in morphology and smallest in size. These findings indicate that a niche shift occurred in coyotes at the Pleistocene/Holocene boundary - from a hunter of large prey to a small prey/more omnivorous animal. Species interactions between Canis were the most likely cause of this transition. This study shows that the Pleistocene extinction event affected species that did not go extinct as well as those that did.

Characterization of docosahexaenoic acid (DHA)-induced heme oxygenase-1 (HO-1) expression in human cancer cells: the importance of enhanced BTB and CNC homology 1 (Bach1) degradation.

The effect of docosahexaenoic acid (DHA) on heme oxygenase-1 (HO-1) expression in cancer cells has never been characterized. This study examines DHA-induced HO-1 expression in human cancer cell model systems. DHA enhanced HO-1 gene expression in a time- and concentration-dependent manner, with maximal induction at 21 h of treatment. This induction of HO-1 expression was confirmed in vivo using a xenograft nude mouse model fed a fish-oil-enriched diet. The increase in HO-1 gene transcription induced by DHA was significantly attenuated by the antioxidant N-acetyl cysteine, suggesting the involvement of oxidative stress. This was supported by direct measurement of lipid peroxide levels after DHA treatment. Using a human HO-1 gene promoter reporter construct, we identified two antioxidant response elements (AREs) that mediate the DHA-induced increase in HO-1 gene transcription. Knockdown of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) expression compromised the DHA-induced increase in HO-1 gene transcription, indicating the importance of the Nrf2 pathway in this event. However, the nuclear protein levels of Nrf2 remained unchanged upon DHA treatment. Further studies demonstrated that DHA reduces nuclear Bach1 protein expression by promoting its degradation and attenuates Bach1 binding to the AREs in the HO-1 gene promoter. In contrast, DHA enhanced Nrf2 binding to the AREs without affecting nuclear Nrf2 expression levels, indicating a new cellular mechanism that mediates DHA's induction of HO-1 gene transcription. To our knowledge, this is the first characterization of DHA-induced HO-1 expression in human malignant cells.

Zinc protoporphyrin suppresses cancer cell viability through a heme oxygenase-1-independent mechanism: the involvement of the Wnt/ß-catenin signaling pathway.

Zinc protoporphyrin (ZnPP), a known inhibitor of heme oxygenase-1 (HO-1), has been reported to have anticancer activity in both in vitro and in vivo model systems. While the mechanisms of ZnPP's anticancer activity remain to be elucidated, it is generally believed that ZnPP suppresses tumor growth through inhibition of HO-1 activity. We examined this hypothesis by altering cellular levels of HO-1 in human ovarian (A2780) and prostate cancer (DU145) cells and found that ZnPP inhibits cancer cell viability through an HO-1-independent mechanism. Neither over-expression nor knockdown of HO-1 significantly alters ZnPP's cytotoxicity in human cancer cells, indicating that HO-1 does not mediate ZnPP's inhibitory effect on cancer cell growth. Consistent with these observations, tin protoporphyrin (SnPP), a well-established HO-1 inhibitor, was found to be much less cytotoxic than ZnPP, and docosahexaenoic acid (DHA), an HO-1 inducer, enhanced ZnPP's cytotoxicity. In an effort to define the mechanisms of ZnPP-induced cytotoxicity, we found that ZnPP but not SnPP, diminished ß-catenin expression through proteasome degradation and potently suppressed ß-catenin-mediated signaling in our model systems. Thus, ZnPP-induced cytotoxicity is independent of HO-1 expression in cancer cells and the Wnt/ß-catenin pathway is potentially involved in ZnPP's anticancer activity.